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Age-related differences in lower limb joint moment (JM), and joint power (JP) during turning remain unclear. The present study investigated age-related differences in lower limb JM and JP during turning between young adults (YAs) and old adults (OAs). We introduced the hierarchical Bayesian inference for comparing and identifying differences in JM, angular velocity(ω), and JP at each stance phase in the two age groups. This study included 16 healthy YAs and 16 healthy OAs (8 men and 8 women in each group). Participants performed 90° step turns to the right at a self-selected natural speed. On comparing the age groups, during 90° step turning, the OA group exhibited larger extention hip JM and JP to control (brake) the upper body in the sagittal plane, exhibited larger abductor moment in each lower limb joint for preventing the body from leaning in the frontal plane during the mid-stance phase, and exhibited larger hip JP and ω and smaller ankle JM in the transverse plane to rotate the body during the mid-stance phase. Our findings suggested that the overall reliance on the hip joint to control body motion in each anatomical plane during step turning is higher in the OA group than in the YA group. In addition, the hierarchical Bayesian inference is useful for comparing the time courses of JM, ω, and JP.

A patient with hypoplastic left heart syndrome developed heart failure due to tachycardia‐induced cardiomyopathy from junctional ectopic tachycardia. Conventional antiarrhythmic therapy was ineffective, but ivabradine successfully controlled the arrhythmia and improved both ventricular function and heart failure.

Congenital cytomegalovirus (cCMV) infection can damage the central nervous system in infants; however, its prognosis cannot be predicted from clinical evaluations at the time of birth. Urinary exosomes can be used to analyze neuronal damage in neuronal diseases. To investigate the extent of neuronal damage in patients with cCMV, exosomal miRNA expression in the urine was investigated in cCMV-infected infants and controls. Microarray analysis of miRNA was performed in a cohort of 30 infants, including 11 symptomatic cCMV (ScCMV), 7 asymptomatic cCMV (AScCMV), and one late-onset ScCMV cases, and 11 healthy controls (HC). Hierarchical clustering analysis revealed the distinct expression profile of ScCMV. The patient with late-onset ScCMV was grouped into the ScCMV cluster. Pathway enrichment analysis of the target mRNAs differed significantly between the ScCMV and HC groups; this analysis also revealed that pathways related to brain development were linked to upregulated pathways. Six miRNAs that significantly different between groups (ScCMV vs. HC and ScCMV vs. AScCMV) were selected for digital PCR in another cohort for further validation. Although these six miRNAs seemed insufficient for predicting ScCMV, expression profiles of urine exosomal miRNAs can reveal neurological damage in patients with ScCMV compared to those with AcCMV or healthy infants.

Epstein-Barr virus (EBV) infection can lead to infectious mononucleosis (EBV-IM) and, more rarely, EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which is characterized by a life-threatening hyperinflammatory cytokine storm with immune dysregulation. Interferon-gamma (IFNγ) has been identified as a critical mediator for primary HLH; however, the detailed role of IFNγ and other cytokines in EBV-HLH is not fully understood. In this study, we used single-cell RNA sequencing to characterize the immune landscape of EBV-HLH and compared it with EBV-IM. Three pediatric patients with EBV-HLH with different backgrounds, one with X-linked lymphoproliferative syndrome type 1 (XLP1), two with chronic active EBV disease (CAEBV), and two patients with EBV-IM were enrolled. The TUBA1B + STMN1 + CD8 + T cell cluster, a responsive proliferating cluster with rich mRNA detection, was explicitly observed in EBV-IM, and the upregulation of SH2D1A—the gene responsible for XLP1—was localized in this cluster. This proliferative cluster was scarcely observed in EBV-HLH cases. In EBV-HLH cases with CAEBV, upregulation of LAG3 was observed in EBV-infected cells, which may be associated with an impaired response by CD8 + T cells. Additionally, genes involved in type I interferon (IFN) signaling were commonly upregulated in each cell fraction of EBV-HLH, and activation of type II IFN signaling was observed in CD4 + T cells, natural killer cells, and monocytes but not in CD8 + T cells in EBV-HLH. In conclusion, impaired responsive proliferation of CD8 + T cells and upregulation of type I IFN signaling were commonly observed in EBV-HLH cases, regardless of the patients’ background, indicating the key features of EBV-HLH.

The introduction of varicella vaccines into routine pediatric immunization programs has led to a considerable reduction in varicella incidence. However, there have been reports of varicella, herpes zoster, and meningitis caused by the vaccine strain of varicella-zoster virus (VZV), raising concerns. Establishing the relationship between the wild-type and vaccine strains in VZV infections among previously vaccinated individuals is crucial. Differences in the single nucleotide polymorphisms (SNPs) among vaccine strains can be utilized to identify the strain. In this study, we employed nanopore sequencing to identify VZV strains and analyzed clinical samples. We retrospectively examined vesicle and cerebrospinal fluid samples from patients with VZV infections. One sample each of the wild-type and vaccine strains, previously identified using allelic discrimination real-time PCR and direct sequencing, served as controls. Ten samples with undetermined VZV strains were included. After DNA extraction, a long PCR targeting the VZV ORF62 region was executed. Nanopore sequencing identified SNPs, allowing discrimination between the vaccine and wild-type strains. Nanopore sequencing confirmed SNPs at previously reported sites (105,705, 106,262, 107,136, and 107,252), aiding in distinguishing between wild-type and vaccine strains. Among the ten unknown samples, nine were characterized as wild strains and one as a vaccine strain. Even in samples with low VZV DNA levels, nanopore sequencing was effective in strain identification. This study validates that nanopore sequencing is a reliable method for differentiating between the wild-type and vaccine strains of VZV. Its ability to produce long-read sequences is remarkable, allowing simultaneous confirmation of known SNPs and the detection of new mutations. Nanopore sequencing can serve as a valuable tool for the swift and precise identification of wild-type and vaccine strains and has potential applications in future VZV surveillance.

Purpose A four-parameter risk model that included cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters was recently developed for prediction of 2-year cardiac mortality risk in patients with chronic heart failure. We sought to validate the ability of this risk model to predict post-discharge clinical outcomes in patients with acute decompensated heart failure (ADHF) and to compare its prognostic value with that of the Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines-Heart Failure (GWTG-HF) risk scores. Methods We studied 407 consecutive patients who were admitted for ADHF and survived to discharge, with definitive 2-year outcomes (death or survival). Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk was calculated using four parameters, namely age, left ventricular ejection fraction, New York Heart Association functional class, and cardiac MIBG heart-to-mediastinum ratio on delayed images. Patients were stratified into three groups based on the 2-year cardiac mortality risk: low- (< 4%), intermediate- (4–12%), and high-risk (> 12%) groups. The ADHERE and GWTG-HF risk scores were also calculated. Results There was a significant difference in the incidence of cardiac death among the three groups stratified using the 2-year cardiac mortality risk model ( p  < 0.0001). The 2-year cardiac mortality risk model had a higher C-statistic (0.732) for the prediction of cardiac mortality than the ADHERE and GWTG-HF risk scores. Conclusion The 2-year MIBG-based cardiac mortality risk model is useful for predicting post-discharge clinical outcomes in patients with ADHF. Trial registration number UMIN000015246, 25 September 2014.

Methyl indole‐2‐acetate is a key structural motif in plant‐derived indole alkaloids. In this study, a mild and efficient protocol is presented for its preparation using readily available aniline derivatives, which are synthesized from malonic esters. The reaction proceeds via an allenyl ester intermediate, with NaCN‐mediated indole formation occurring at ambient temperature, affording high yields and broad substrate scope. The synthetic utility of this approach is demonstrated through the asymmetric total synthesis of geissoschizoline, a Strychnos‐type monoterpenoid indole alkaloid. This synthesis not only establishes a novel route to monoterpenoid indole alkaloids but also achieves complete stereochemical control in constructing the six chiral centers of the natural product. An indole synthesis via an allenyl ester intermediate at ambient temperature has been developed. The mild reaction conditions allow the use of a broad range of substrates. Notably, the utility of this approach is demonstrated through the asymmetric total synthesis of geissoschizoline, a Strychnos‐type monoterpenoid indole alkaloid. This synthesis highlights a novel strategy for accessing monoterpenoid indole alkaloids.

Background and Aims Interactions between the lung microbiome and pulmonary epithelium plays a pivotal role in shaping immunity in the lung. Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease (ILD). Some patients with IPF develop episodic acute exacerbations often associated with microbial dysbiosis in the lungs. This study aimed to investigate etiologic agents as well as the lung microbiome in patients with ILDs and sarcoidosis. Methods This study analyzed 31 patients divided into the IPF (IPF‐stable, n = 12), acute exacerbation of ILDs (AE‐ILDs, n = 6), and sarcoidosis (n = 13) groups. Bronchoalveolar lavage fluid (BALF) samples were analyzed by RNA‐based metagenomic next‐generation sequencing (NGS) on an Illumina platform. Results In total, 87 pathogens were detected using metagenomic NGS at the genus level. Prevotella, Streptococcus, and Veillonella dominated the BALF microbial communities, and sequence reads of these bacteria were abundant, especially in the sarcoidosis group. Conversely, only a small number of bacterial reads were detected in the AE‐ILDs group, and the overall proportion of microbial composition differed from that of the other groups. No significant difference was found in community diversity (α‐diversity) among the groups, whereas the structural similarity of the microflora (β‐diversity) differed significantly between the AE‐ILDs and sarcoidosis groups. Conclusions Bacterial sequence reads in BALF were smaller in both the IPF‐stable and AE‐ILD groups than in the sarcoidosis group. Dysbiosis in the lung microbiome has been observed in patients with AE‐ILD and may be related to the progression of inflammation.

During the culture of Escherichia coli BW25113 grown on glucose as a carbon source, approximately 1.0 g acetate/l was produced after 10 h and, thereafter, acetate was completely consumed as an alternative carbon source after glucose starvation. In contrast, during the culture of a yggG -deficient E. coli mutant JW2903, acetate also accumulated but was not subsequently consumed, even after glucose starvation during the culture for 24 h. The analysis of gene expression revealed that the accumulation of acetate was not due to the malfunction of the acetate-assimilating pathway in response to glucose starvation but to the lowering of metabolic flow into the TCA cycle. This was explained by the lower levels of gltA and acnA gene expressions, and the higher level of arcA gene in JW2903 cells. These results suggest that the yggG gene contributes to the normalization of metabolic pathways including the TCA cycle.